Diwakar Jain

The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes ☆

OBJECTIVES The purpose of this study was to assess safety and efficacy of enhanced external counterpulsation (EECP). BACKGROUND Case series have shown that EECP can improve exercise tolerance, symptoms and myocardial perfusion in stable angina pectoris. METHODS A multicenter, prospective, randomized, blinded, controlled trial was conducted in seven university hospitals in 139 outpatients with angina, documented coronary artery disease (CAD) and positive exercise treadmill test. Patients were given 35 h of active counterpulsation (active CP) or inactive counterpulsation (inactive CP) over a four- to seven-week period. Outcome measures were exercise duration and time to > or =1-mm ST-segment depression, average daily anginal attack count and nitroglycerin usage. RESULTS Exercise duration increased in both groups, but the between-group difference was not significant (p > 0.3). Time to > or =1-mm ST-segment depression increased significantly from baseline in active CP compared with inactive CP (p = 0.01). More active-CP patients saw a decrease and fewer experienced an increase in angina episodes as compared with inactive-CP patients (p < 0.05). Nitroglycerin usage decreased in active CP but did not change in the inactive-CP group. The between-group difference was not significant (p > 0.7). CONCLUSIONS Enhanced external counterpulsation reduces angina and extends time to exercise-induced ischemia in patients with symptomatic CAD. Treatment was relatively well tolerated and free of limiting side effects in most patients.

Annexin-V imaging for noninvasive detection of cardiac allograft rejection

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Single photon-emission computed tomography

The current document is an update of an earlier version of single photon emission tomography (SPECT) guidelines that was developed by the American Society of Nuclear Cardiology. Although that document was only published a few years ago, there have been significant advances in camera technology, imaging protocols, and reconstruction algorithms that prompted the need for a revised document. This publication is designed to provide imaging guidelines for physicians and technologists who are qualified to practice nuclear cardiology. While the information supplied in this document has been carefully reviewed by experts in the field, the document should not be considered medical advice or a professional service. We are cognizant that SPECT technology is evolving rapidly and that these recommendations may need further revision in the near future. Hence, the imaging guidelines described in this publication should not be used in clinical studies until they have been reviewed and approved by qualified physicians and technologists from their own particular institutions. 2. INSTRUMENTATION QUALITY ASSURANCE AND PERFORMANCE

Emotional and Physical Precipitants of Ventricular Arrhythmia

Background—Observational studies have suggested that psychological stress increases the incidence of sudden cardiac death. Whether emotional or physical stressors can trigger spontaneous ventricular arrhythmias in patients at risk has not been systematically evaluated. Methods and Results—Patients with implantable cardioverter-defibrillators (ICDs) were given diaries to record levels of defined mood states and physical activity, using a 5-point intensity scale, during 2 periods preceding spontaneously occurring ICD shocks (0 to 15 minutes and 15 minutes to 2 hours) and during control periods 1 week later. ICD-stored electrograms confirmed the rhythm at the time of shock. A total of 107 confirmed ventricular arrhythmias requiring shock were reported by 42 patients (33 men; mean age, 65 years; 78% had coronary artery disease) between August 1996 and September 1999. In the 15 minutes preceding shock, an anger level ≥3 preceded 15% of events compared with 3% of control periods (P <0.04; odds ratio, 1.83; 95% confidence intervals, 1.04 to 3.16) Other mood states (anxiety, worry, sadness, happiness, challenge, feeling in control, or interest) did not differ. Patients were more physically active preceding shock than in control periods. Anger and physical activity were independently associated with the preshock period. Conclusions—Anger and physical activity can trigger ventricular arrhythmias in patients with ICDs. Future investigations of therapies aimed at blocking a response to these stressors may decrease ventricular arrhythmias and shocks in these patients.

Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease☆

OBJECTIVES We examined the relationship of the psychological profile to left ventricular dysfunction induced during mental stress. BACKGROUND The contribution of psychological factors to mental stress-provoked silent myocardial ischemia has not been explored. METHODS Thirty patients with chronic stable coronary artery disease and a reversible defect on stress thallium-201 imaging completed a psychological assessment by questionnaire and Structured Interview, serially administered mental stress and brief walking exercise. Blood pressure, electrocardiogram (ECG) and left ventricular indexes were obtained by ambulatory serial radionuclide ventriculography. Silent ventricular dysfunction was defined by a decrease > or = 0.05 in ejection fraction or > or = 1 mm in ST segment on the ECG in the absence of symptoms. RESULTS Of the 30 patients, 15 (Group I) had evidence of silent left ventricular dysfunction during mental arithmetic. The other 15 (Group II) showed no change. In addition, 18 of 30 patients had this dysfunction during the Structured Interview. Both ischemic and nonischemic groups developed comparable and significant increases in heart rate and blood pressure. Group I patients were distinguished by higher scores on measures of aggressive responding (p < 0.001), trait anger (p < 0.0001), hostile affect (p < 0.003) and an index of behavioral reactivity (p < 0.003) and a lower score on anger control (p < 0.001). No other variables, including historical and clinical indexes, discriminated between the two groups. CONCLUSIONS Patients with coronary artery disease and mental stress-provoked silent ventricular dysfunction were distinguished by a psychological profile consistent with emotional reactivity to social interaction and mental provocation, with anger as the predominant affective state. Patients with such a profile may be at risk of frequent silent left ventricular dysfunction.

Myocardial Perfusion Imaging With 99mTc Tetrofosmin Comparison to 201Tl Imaging and Coronary Angiography in a Phase III Multicenter Trial

Background Our objective was to compare the sensitivity and specificity of tetrofosmin, a new 99m Tc-labeled myocardial perfusion imaging agent for the detection of myocardial perfusion abnormalities, with those of 201 Tl and coronary angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging could provide data comparable to those of 201 Tl imaging. Myocardial perfusion imaging plays an important role for the evaluation of coronary artery disease. Newer 99m Tc-labeled agents offer several advantages over 201 Tl, the conventional myocardial perfusion imaging agent. Tetrofosmin is a new 99m Tc-labeled agent with promising results in preliminary studies. Methods and Results Two hundred fifty-two patients with suspected coronary artery disease were enrolled in 10 centers in the United States and Europe. All patients underwent exercise and rest myocardial perfusion imaging with 99m Tc-tetrofosmin using two separate injections of the radiotracer 4 hours apart on the same day. Planar images were obtained in three standard views 15 to 60 minutes after radiotracer injection. Patients also underwent standard exercise and redistribution planar 201 Tl imaging within 2 weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low likelihood of coronary artery disease underwent exercise and rest tetrofosmin imaging. Coronary angiograms were available in 181 patients with suspected coronary artery disease. All radionuclide images were processed in the central core laboratory and interpreted blindly by a panel of four experienced readers. 201 Tl images and tetrofosmin images were read separately. Discrepancies were resolved by consensus. The workload, peak heart rate, and double products were comparable during exercise for both imaging agents. Technically acceptable paired 201 Tl and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin images were generally of good quality, with low extracardiac activity, and easy to interpret. Patients were categorized as showing normal, ischemia, infarction, or mixture with each imaging modality. Precise concordance for each of these categories was 59.4% (κ=0.44; 95% CI, 0.35 to 0.53). When patients were categorized as normal or abnormal, the concordance was 80.4% (κ=0.55; 95% CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior, inferior, lateral, and apical) was categorized as normal versus abnormal, the concordance varied from 81% to 90%. When similar comparison was made for the specific category of abnormality, the concordance was 64% to 84%. When coronary angiography was used as the criterion, the sensitivity and positive and negative predictive accuracy of tetrofosmin and 201 Tl were comparable. The normalcy rate of tetrofosmin images in the healthy subjects with low likelihood of coronary artery disease was 97%. Conclusions 99m Tc tetrofosmin is a new myocardial imaging agent with favorable imaging characteristics with results comparable to those of 201 Tl.Background Our objective was to compare the sensitivity and specificity of tetrofosmin, a new 99m Tc-labeled myocardial perfusion imaging agent for the detection of myocardial perfusion abnormalities, with those of 201 Tl and coronary angiography. Our hypothesis was that same-day stress/rest tetrofosmin imaging could provide data comparable to those of 201 Tl imaging. Myocardial perfusion imaging plays an important role for the evaluation of coronary artery disease. Newer 99m Tc-labeled agents offer several advantages over 201 Tl, the conventional myocardial perfusion imaging agent. Tetrofosmin is a new 99m Tc-labeled agent with promising results in preliminary studies. Methods and Results Two hundred fifty-two patients with suspected coronary artery disease were enrolled in 10 centers in the United States and Europe. All patients underwent exercise and rest myocardial perfusion imaging with 99m Tc-tetrofosmin using two separate injections of the radiotracer 4 hours apart on the same day. Planar images were obtained in three standard views 15 to 60 minutes after radiotracer injection. Patients also underwent standard exercise and redistribution planar 201 Tl imaging within 2 weeks of tetrofosmin imaging. In addition, 58 healthy subjects with low likelihood of coronary artery disease underwent exercise and rest tetrofosmin imaging. Coronary angiograms were available in 181 patients with suspected coronary artery disease. All radionuclide images were processed in the central core laboratory and interpreted blindly by a panel of four experienced readers. 201 Tl images and tetrofosmin images were read separately. Discrepancies were resolved by consensus. The workload, peak heart rate, and double products were comparable during exercise for both imaging agents. Technically acceptable paired 201 Tl and tetrofosmin images were available in 224 of 252 patients. Tetrofosmin images were generally of good quality, with low extracardiac activity, and easy to interpret. Patients were categorized as showing normal, ischemia, infarction, or mixture with each imaging modality. Precise concordance for each of these categories was 59.4% (κ=0.44; 95% CI, 0.35 to 0.53). When patients were categorized as normal or abnormal, the concordance was 80.4% (κ=0.55; 95% CI, 0.43 to 0.67). When each of five anatomic territories (septal, anterior, inferior, lateral, and apical) was categorized as normal versus abnormal, the concordance varied from 81% to 90%. When similar comparison was made for the specific category of abnormality, the concordance was 64% to 84%. When coronary angiography was used as the criterion, the sensitivity and positive and negative predictive accuracy of tetrofosmin and 201 Tl were comparable. The normalcy rate of tetrofosmin images in the healthy subjects with low likelihood of coronary artery disease was 97%. Conclusions 99m Tc tetrofosmin is a new myocardial imaging agent with favorable imaging characteristics with results comparable to those of 201 Tl.

Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease

OBJECTIVES We sought to investigate the mechanism of a mental stress-induced fall in left ventricular ejection fraction (LVEF) in patients with coronary artery disease. BACKGROUND Mental stress induces a fall in LVEF in a significant proportion of patients with coronary artery disease. This is accompanied by an increase in heart rate, blood pressure and rate-pressure product. Whether the mental stress-induced fall in LVEF is due to myocardial ischemia, altered loading conditions or a combination of both is not clear. METHODS Left ventricular (LV) function was studied noninvasively by serial equilibrium radionuclide angiocardiography and simultaneous measurement of peak power, a relatively afterload-independent index of LV contractility, in 21 patients with coronary artery disease (17 men, 4 women) and 9 normal subjects (6 men, 3 women) at baseline, during mental stress and during exercise. Peripheral vascular resistance (PVR), cardiac output (CO), arterial and end-systolic ventricular elastance (Ea, Ees,) and ventriculoarterial coupling (V/AC) were also calculated. Patients underwent two types of mental stress-mental arithmetic and anger recall-as well as symptom-limited semisupine bicycle exercise. RESULTS Nine patients (43%) had an absolute fall in LVEF of > or = 5% (Group I) in response to at least one of the mental stressors, whereas the remaining patients did not (Group II). Group I and Group II patients were similar in terms of baseline characteristics. Both groups showed a significant but comparable increase in systolic blood pressure (15+/-7 vs. 9+/-10 mm Hg, p=0.12) and a slight increase in heart rate (7+/-4 vs. 8+/-7 beats/min, p=0.6) and a comparable increase in rate-pressure product (2.2+/-0.9 vs. 1.9+/-1.2 beats/min x mm Hg, p=0.6) with mental stress. However, PVR increased in Group I and decreased in Group II (252+/-205 vs. -42+/-230 dynes x s x cm(-5), p=0.006), and CO decreased in Group I and increased in Group II (-0.2+/-0.4 vs. 0.6+/-0.7 liters/min, p=0.02) with mental stress. There was no difference in the change in peak power (p=0.4) with mental stress. With exercise, an increase in systolic blood pressure, heart rate, rate-pressure product and CO and a fall in PVR were similar in both groups. Of the two mental stressors, anger recall resulted in a greater fall in LVEF and a greater increase in diastolic blood pressure. Exercise resulted in a fall in LVEF in 7 patients (33%). However, exercise-induced changes in LVEF and hemodynamic variables were not predictive of mental stress-induced changes in LVEF and hemodynamic variables. Conclusions. Abnormal PVR and Ea responses to mental stress and exercise are observed in patients with a mental stress-induced fall in LVEF. Peripheral vasoconstrictive responses to mental stress contribute significantly toward a mental stress-induced fall in LVEF.

Trends in incidence, management, and outcomes of cardiogenic shock complicating ST-elevation myocardial infarction in the United States.

Background Limited information is available on the contemporary and potentially changing trends in the incidence, management, and outcomes of cardiogenic shock complicating ST‐elevation myocardial infarction (STEMI). Methods and Results We queried the 2003–2010 Nationwide Inpatient Sample databases to identify all patients ≥40 years of age with STEMI and cardiogenic shock. Overall and age‐, sex‐, and race/ethnicity‐specific trends in incidence of cardiogenic shock, early mechanical revascularization, and intra‐aortic balloon pump use, and inhospital mortality were analyzed. From 2003 to 2010, among 1 990 486 patients aged ≥40 years with STEMI, 157 892 (7.9%) had cardiogenic shock. The overall incidence rate of cardiogenic shock in patients with STEMI increased from 6.5% in 2003 to 10.1% in 2010 (Ptrend<0.001). There was an increase in early mechanical revascularization (30.4% to 50.7%, Ptrend<0.001) and intra‐aortic balloon pump use (44.8% to 53.7%, Ptrend<0.001) in these patients over the 8‐year period. Inhospital mortality decreased significantly, from 44.6% to 33.8% (Ptrend<0.001; adjusted OR, 0.71; 95% CI, 0.68 to 0.75), whereas the average total hospital cost increased from

Technetium-99m labeled myocardial perfusion imaging agents

35 892 to

Direct Imaging of Exercise-Induced Myocardial Ischemia With Fluorine-18–Labeled Deoxyglucose and Tc-99m-Sestamibi in Coronary Artery Disease

45 625 (Ptrend<0.001) during the study period. There was no change in the average length of stay (Ptrend=0.394). These temporal trends were similar in patients <75 and ≥75 years of age, men and women, and across each racial/ethnic group. Conclusions The incidence of cardiogenic shock complicating STEMI has increased during the past 8 years together with increased use of early mechanical revascularization and intra‐aortic balloon pumps. There has been a concomitant decrease in risk‐adjusted inhospital mortality, but an increase in total hospital costs during this period.